The epidermis of the skin is composed of stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Among them, the stratum corneum is one of the most important portions in the body, which exists in an outermost layer of the skin and serves to prevent water loss and serves as a primary defense against harmful contaminants in an external environment.
The stratum corneum is largely composed of keratinocytes and stratum corneum intercellular lipids. Here, the keratinocytes, which are cells differentiated and formed from the stratum basale of the epidermis, are composed of protein called keratin, and the stratum corneum intercellular lipids are filled between the keratinocytes. The stratum corneum intracellular lipids are mainly composed of ceramide, cholesterol, fatty acids, and the like. In the normal skin, the stratum corneum intracellular lipids exist in a multi-lamellar structure, and it is known that the multi-lamellar structure is a physical basis of significantly low material permeability of the skin. The low permeability as described above is an important factor of an epidermal permeability barrier function of the skin. In addition, a skin barrier function may perform roles of moisturizing the skin and physically, chemically, and microbiologically protecting the skin, and the like.
A theory about structural features of the stratum corneum and roles of constituting components depending on the structural features, particularly, roles of the stratum corneum intercellular lipids having the multi-lamellar structure has been initially suggested by Peter M. Elias (Department of Dermatology, San Francisco State University), through a “brick and mortar model” in 1970s, and thereafter, availability of this model has been proven through various follow-up researches (The Characterization of Molecular Organization of Multi-lamellar Emulsions Containing Pseudoceramide and Type III Synthetic Ceramide. J. Invest. Dermatol. 2003 October; 121(4):794-801.).
A drug delivery system is a medical technology of minimizing adverse effects of a drug and maximizing efficacy and an effect thereof to allow the required amount of the drug to be efficiently delivered. The drug is delivered through various routes such as an oral route, a parenteral route, a transdermal route, a mucosal route, a transplant route, and the like. Among them, in a case of administering the drug through the transdermal route, it may be easy to adjust an administration dose of the drug, there is no systemic effect, and bioavailability of the drug may be increased by preventing drug denaturation generated at the time of intestinal absorption.
As described above, the multi-lamellar structure of the stratum corneum intercellular lipids becomes a physical basis of significantly low permeability of the skin. However, in a transdermal drug delivery system or topical formulation, the low permeability as described above has been a large obstacle in developing effective formulations. In the development of the transdermal drug delivery system or topical formulation up to now, as a method of overcoming the problem as described above, a method of physically or chemically changing or destroying the multi-lamellar structure of the stratum corneum intracellular lipids, or the like, has been used.
In the transdermal drug delivery system, a delivery route of the drug through the stratum corneum is subjected to a series of the following processes:
1) a drug is dissolved from a vehicle,
2) the dissolved drug is partitioned into the stratum corneum, particularly, stratum corneum intercellular lipids,
3) the drug passes through the stratum corneum while being diffused through the stratum corneum intercellular lipids,
4) the drug moves to the stratum granulosum while being partitioned in a boundary portion between the stratum corneum and the stratum granulosum, and
5) the drug is diffused to the stratum granulosum, the stratum spinosum, and the stratum basale again. It may be explained from the process as described above that after dissolution of the drug from the matrix, a process of “partitioning-diffusion” is repeated. Partitioning of drug in the stratum corneum is changed depending on partition coefficient of the drug between the matrix and the stratum corneum, in more detail, between the stratum corneum intercellular lipids.
The present inventors developed a composition having a multi-lamellar structure similar to that of the stratum corneum intercellular lipids through a prior study, and it was confirmed that this composition assisted in reinforcing and repairing a skin barrier function. The present inventors found that since this composition has a structure similar to that of the stratum corneum intercellular lipids, in a case of a topical formulation using the corresponding composition as a matrix, a primary partitioning process (partitioning of drug between the matrix and the stratum corneum) of the above-mentioned transdermal drug delivery system may be effectively promoted, such that the partitioning of the drug in the stratum corneum is increased, and as a result, a content of the drug in the stratum corneum is increased, thereby completing the present invention.